comparison of combination chemotherapy regimens in treating patients with ewing's sarcoma or neuroectodermal tumor

Conditions: Sarcoma

Summary: rationale: drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. it is not yet known which chemotherapy regimen combined with radiation therapy and/or surgery is more effective in treating ewing's sarcoma or primitive neuroectodermal tumor. purpose: randomized phase iii trial to compare the effectiveness of different chemotherapy regimens combined with radiation therapy and/or surgery in treating patients who have ewing's sarcoma or primitive neuroectodermal tumor.

objectives: * compare the effect of interval-compressed vs standard chemotherapy in terms of event-free survival and overall survival in patients with newly diagnosed, localized ewing's sarcoma or peripheral primitive neuroectodermal tumor. outline: this is a randomized, multicenter study. patients are stratified according to age (under 18 years vs 18 years and over) and location of primary disease (pelvic vs nonpelvic). patients are randomized to 1 of 2 treatment arms for induction and continuation therapy. * induction therapy (weeks 1-12): * arm i: patients receive alternating courses of chemotherapy consisting of vincristine iv on day 1, doxorubicin iv continuously over 48 hours on days 1 and 2, and cyclophosphamide iv over 1 hour on day 1 for courses 1 and 3 and ifosfamide iv over 1 hour and etoposide iv over 1-2 hours on days 1-5 for courses 2 and 4. beginning 24 hours after the last dose of chemotherapy for each course, patients receive filgrastim (g-csf) subcutaneously (sc) daily until blood counts recover. treatment continues every 3 weeks for 4 courses. * arm ii: patients receive alternating courses of chemotherapy consisting of vincristine, doxorubicin, and cyclophosphamide as in arm i for courses 1, 3, and 5 and ifosfamide and etoposide as in arm i for courses 2, 4, and 6. patients also receive g-csf as in arm i. treatment continues every 2 weeks for 6 courses. after completion of induction therapy, patients in both arms receive local control treatment to the primary tumor. patients receive continuation chemotherapy after surgery or concurrently with radiotherapy. * continuation therapy: * arm i (weeks 13-42): patients receive additional alternating courses of chemotherapy as in arm i of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 7 and/or 11 and/or 13. patients also receive g-csf as in induction therapy. treatment continues every 3 weeks for 10 courses. * arm ii (weeks 13-29): patients receive additional alternating courses of chemotherapy as in arm ii of induction therapy with the exception of vincristine and cyclophosphamide alone for courses 9 and/or 11 and/or 13. patients also receive g-csf as in induction therapy. treatment continues every 2 weeks for 8 courses. patients are followed every 3 months for 4 years and then every 6 months for 1 year. projected accrual: approximately 528 patients will be accrued for this study within 4-5 years.

Eligibility criteria:
disease characteristics: * histologically confirmed localized ewing's sarcoma or peripheral primitive neuroectodermal tumor (pnet) of the bone or soft tissues * diagnostic biopsy of primary tumor within 30 days of study * paraspinal or bony skull tumors of extradural origin allowed * no intradural soft tissue tumors * askin's tumor of the chest wall allowed * chest wall tumors with ipsilateral pleural effusions or ipsilateral pleural-based secondary tumor nodules allowed * no contralateral pleural effusions * no metastatic disease or distant node involvement * one pulmonary or pleural nodule greater than 1 cm in diameter or more than 1 nodule greater than 0.5 cm in diameter are considered pulmonary metastasis * solitary lung nodules of 0.5-1 cm or multiple nodules of 0.3-0.5 cm allowed unless biopsy positive for tumor * light microscopic appearance (hematoxylin and eosin stained) consistent with ewing's sarcoma or peripheral pnet * no immunohistochemical or ultrastructural evidence of rhabdomyosarcoma * no esthesioneuroblastoma * clinically or pathologically involved regional lymph nodes allowed * no cns involvement patient characteristics: age: * 50 and under at diagnosis performance status: * not specified life expectancy: * not specified hematopoietic: * not specified hepatic: * bilirubin no greater than 1.5 mg/dl renal: * creatinine normal for age * creatinine clearance or isotope glomerular filtration rate at least 75 ml/min cardiovascular: * shortening fraction at least 28% by echocardiography or * ejection fraction at least 55% by radionuclide angiogram other: * not pregnant or nursing * fertile patients must use effective contraception * no other prior malignancy except skin cancer diagnosed at least 5 years ago and currently in remission prior concurrent therapy: biologic therapy: * no prior immunotherapy for skin cancer * no concurrent sargramostim (gm-csf) * no concurrent pegfilgrastim chemotherapy: * no prior chemotherapy endocrine therapy: * not specified radiotherapy: * no prior radiotherapy surgery: * prior complete or partial excision of primary tumor allowed

Keywords: localized ewing sarcoma/peripheral primitive neuroectodermal tumor